TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends.
TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends.
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DOI：
10.1074/jbc.m116.719021
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发表时间：
2016-09-23
期刊：
影响因子：
--
通讯作者：
Shimizu S
中科院分区：
文献类型：
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作者：
Konishi A;Izumi T;Shimizu S
哺乳动物的染色体末端由一种称为端粒的特殊核蛋白复合物保护。端粒特异性多蛋白复合物shelterin和更高级的端粒染色质结构结合联合收割机以稳定染色体末端。在这里，我们表明，TRF 2，shelterin的一个组成部分，结合到核心组蛋白，以保护染色体末端不适当的DNA损伤反应和端粒DNA的损失。TRF 2的N-末端Gly/Arg富集结构域（GAR结构域）直接结合核心组蛋白的球状结构域。这种相互作用需要TRF 2的GAR结构域中的保守精氨酸残基。这些精氨酸残基被丙氨酸取代的TRF 2突变体失去了保护端粒的能力，并诱导端粒的环结构的端粒染色质的切割引起的快速端粒缩短。这些发现显示了先前未注意到的shelterin复合物和核小体组蛋白之间的相互作用，以稳定染色体末端。
Mammalian chromosome ends are protected by a specialized nucleoprotein complex called telomeres. Both shelterin, a telomere-specific multi-protein complex, and higher order telomeric chromatin structures combine to stabilize the chromosome ends. Here, we showed that TRF2, a component of shelterin, binds to core histones to protect chromosome ends from inappropriate DNA damage response and loss of telomeric DNA. The N-terminal Gly/Arg-rich domain (GAR domain) of TRF2 directly binds to the globular domain of core histones. The conserved arginine residues in the GAR domain of TRF2 are required for this interaction. A TRF2 mutant with these arginine residues substituted by alanine lost the ability to protect telomeres and induced rapid telomere shortening caused by the cleavage of a loop structure of the telomeric chromatin. These findings showed a previously unnoticed interaction between the shelterin complex and nucleosomal histones to stabilize the chromosome ends.